The objective of the proposed research program is a thorough understanding of the ionic conductance of neuron cell body membranes. The cell body is specialized for integration of incoming information and for spike initiation, functions not shared by axons. Consequently, the ionic conductances of cell body membrane differ qualitatively and quantitatively from those of axons. The axon has been studied intensely, but study of cell body membrane is only beginning. Our emphasis centers on the roles of Ca ions as cytoplasmic second messengers controlling ion permeability at the membrane. We are approaching the study of the importance of Ca ions in excitability by studying molluscan neurons using voltage clamp. We are interested in 1) the Ca ions conductance of the membrane, and the role of Ca ions current in spike production, 2) the time course and metabolic control of internal Ca ions concentration transients near the membrane during activity, 3) the activation mechanism of Ca ions dependent potassium conductance, and 4) the use-dependent inactivation of potassium conductance. This work will provide new and valuable information about the mechanisms controlling cell body membrane conductances and about cytoplasmic Ca ions metabolism. Strong analogies can be drawn between the molluscan cells we are studying and other types of cells such as mammalian spinal motoneurons and cardiac Purkinje and myocardial cells. The results of our study may possibly be generalized to provide a basic description of the properties and capabilities of the integrating membrane of neurons.